Helt-KO Mouse

Helt, also known as Megane and Heslike, is a basic helix-loop-helix transcriptional repressor. It plays a crucial role in determining GABAergic over glutamatergic neuronal fate in the developing mesencephalon. Helt is involved in a network of basic helix-loop-helix transcription factors and may regulate neuronal differentiation and/or identity [1,2].

In Helt-deficient mouse embryos, GABAergic neurons in the mesencephalon were mostly absent, and glutamatergic neurons emerged instead. Conversely, ectopic expression of Helt suppressed glutamatergic formation and induced GABAergic neurogenesis. This indicates that Helt determines the neurotransmitter phenotype in the mesencephalon. Moreover, Helt was found to repress proneural genes Ngn1 and Ngn2, which are selectively expressed in glutamatergic progenitors and confer the glutamatergic fate, suggesting Helt's role in this fate-determination process [1].

In conclusion, Helt is essential for determining the balance between GABAergic and glutamatergic neuronal fates in the developing mesencephalon. The gene knockout mouse models have been instrumental in revealing Helt's role in this important neural developmental process, which may have implications for understanding neurological development and related disorders [1].

References:

1. Nakatani, Tomoya, Minaki, Yasuko, Kumai, Minoru, Ono, Yuichi. 2007. Helt determines GABAergic over glutamatergic neuronal fate by repressing Ngn genes in the developing mesencephalon. In Development (Cambridge, England), 134, 2783-93. doi:. https://pubmed.ncbi.nlm.nih.gov/17611227/

2. Nakatani, Tomoya, Mizuhara, Eri, Minaki, Yasuko, Sakamoto, Yoshimasa, Ono, Yuichi. 2004. Helt, a novel basic-helix-loop-helix transcriptional repressor expressed in the developing central nervous system. In The Journal of biological chemistry, 279, 16356-67. doi:. https://pubmed.ncbi.nlm.nih.gov/14764602/